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G3 McLean W, Boucher EA, Brennan M, et al. Is there an indication for the use of barbiturate-containing analgesic agents in the treatment of pain? Guidelines for their safe use and withdrawal
management. Canadian Pharmacists Association. Can J Clin Pharmacol 2000;7(4):191-197.
Study
McLean 2000
Canada
Systematic Review
Purpose
To provide medical and
pharmaceutical
practitioners with
information on the
effectiveness, safety and
risks associated with
barbiturate-containing
analgesic (BCA) agents
and an approach to
management of
withdrawal from BCAs.
Sources
Search methodology / Databases searched
Background paper: Sellers 1999 (Can J Clin
Pharmacol)
MEDLINE (1967 to 11/1996)
Published and unpublished reports by
Addiction Research Foundation researchers
Canadian manufacturers of BCA products
Inclusion criteria
Barbiturates alone
Barbiturates in combination
-codeine
-caffeine
-acetylsalicylic acid (ASA)
-acetaminophen
-analgesics
-opiates
Exclusion criteria
Not described
Evaluation Methods for Included Studies
Advisory panel reviewed Sellers 1999
Formulated final guidelines (3 year process)
Outcomes considered:
Dependence
Abuse
Addiction
Efficacy
Toxicity
Drugs included (drug/barbiturate component)
Cafergot-PB (phenobarbital)
Fiorinal (butalbital)
Phenaphen with codeine (phenobarbital)
Tecnal (butalbital)
Trianal (butalbital)
Summary
Role of BCAs in the treatment of pain
No evidence exists showing a clinically important
enhancement of analgesic efficacy of BCAs due to the
barbiturate constituents
A recurring clinical question concerning barbiturate
containing products is whether the barbiturate containing
component contributes in some synergistic way to the
analgesia or toxicity of the product.
-there is inconsistent data on whether barbiturates
contribute to enhanced analgesia when combined with
opiates
-studies have shown an increase in sedation without
enhancement of analgesia
-in elderly patients, the addition of a BCA with 3 or more
other medications adds significantly to the risk of toxicity
Safety and risks associated with BCAs
BCAs have the potential to produce drug dependence
and addictive behavior, especially with regular use
In BCA overdose, the barbiturate component is only one
of the clinically significant contributors to any morbidity,
but its presence can complicate the management of
additive or synergistic toxicities.
There are disadvantages to using barbiturates alone
-tolerance
-risk of abuse and dependence
-hangover and other prolonged effects
-interference with metabolism of other drugs
-enhancement by alcohol
-enhancement by other psychoactive depressant drugs
-severe toxic effects of overdose
The data of the safety of the barbiturate in BCA products
are incomplete because well designed studies have not
been done
The question of the intrinsic abuse of butalbital
combination products has not been directly addressed
There are regulatory reports of significant abuse and
safety issues with BCAs
The severity of a withdrawal syndrome produced by
barbiturates is significantly associated with both the
intensity and duration of the preceding barbiturate
exposure
-early, mild, primary manifestations = tremulousness
-later secondary manifestations = seizures and delirium
Summary (continued)
Safety and risks associated with BCAs (continued)
Morbidity and mortality associated with barbiturate
withdrawal syndrome
-increased by delay in recognition
-presence of concurrent medical or surgical illnesses
-concurrent other psychoactive substance use disorders
Lowest acute dose of butalbital alone reported to be lethal
in adults = 2.0 g
No clinical data are available on the interaction of
barbiturates and opiates on respiratory depression;
however they must be assumed to be at lease additive
Recommendations to physicians concerning the use
of BCAs
BCAs are not recommended for patients who present for
initiation of pain management
Patients taking BCAs for intermittent treatment of acute
pain
-reassess; educate patient
-strongly consider alternative therapy
Patients taking BCAs for continuous treatment of chronic
pain
-reassess and advise patient of value of discontinuation
-strongly consider alternative therapy
Recommendations to pharmacists concerning the use
of BCAs
Ensure the patient is informed of the ingredients and
potential risks of BCAs
Be alert to early indicators of inappropriate use and the
potential for forged prescriptions
Communicate with the prescribe regarding the patient’s
-drug profile information
-pattern of use
-compliance problems
-overuse
Suggest discontinuation of BCAs to current users
Contact the prescriber to recommend safer alternative
therapy for new prescriptions
Page 2 McLean 2000
Summary (continued)
Management of withdrawal from BCAs
There are no data on withdrawal from BCAs
A reasonable management approach would include:
-trial discontinuation only attempted with the patients
cooperation
-single source of prescribed medication required
-slow rather than abrupt discontinuation
-refer to substance abuse specialist if patient does not agree to
discontinue
Recommendations for patient assessment by the physician
Determine pattern and level of use
-history and physical exam
-consultation with pharmacist to determine pattern and level of
use
Assessment of underlying medical condition
Comments
Because BCAs do not have a therapeutic advantage, there is no
clinical reason to choose such a combination product when a simpler
and often less expensive formulation (eg, acetaminophen, acetylsalicylic acid, NSAID, or narcotic) or a more specific anti-migraine
drug (eg, dihydroergotamine or sumatriptan) is available.
Extrapolation from published reports on abuse and withdrawal
syndrome with these drugs suggests that BCAs have the potential to
produce drug dependence and addictive behavior, especially with
regular use.
There is no reason to choose a combination product when a simpler
product may be a safer alternative by minimizing the potential for
addiction and the occurrence of additive side effects or toxicities.
Providers should re-evaluate treatment for patients using BCAs,
following recommendations for management of withdrawal based on
estimated consumption.
Establishment of a diagnosis in order to select an appropriate
alternative therapy
Develop a plan for discontinuation and substitution
Conclusion: No evidence exists to show a clinically important enhancement of analgesic efficacy of BCAs due to the barbiturate constituents. BCAs should be avoided in elderly people.